The first interconversion of a cis-dibenzo[b,d]-pyran to the corresponding trans-isomer was accomplished by Razdan and Zitko when they converted cis-1-hydroxy-3-n-pentyl-6,6,9-trimethyl-6a, 7,8,10a-tetrahydro-6H-dibenzo-[b,d]pyran to the corresponding trans-6a, 7,10,10a-tetrahydro-dibenzo[b,d]pyran derivative. This interconversion was effected by treatment of the cis-isomer with boron tribormide in dichloromethane at -20.degree. C. for ninety minutes. The isomerization was accompanied by a double bond migration of the .DELTA..sup.9 (10) double bond to the .DELTA..sup.8 (9) position. The isomerization reaction of Razdan and Zitko is discussed more fully in Tetrahedron Letters, 4947-4950 (1960).
Treatment of a cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibe nzo [b,d]pyran-9-one, a compound differing from that of Razdan and Zitko by having a tetone group at the C-9 position instead of a methyl group, and a totally saturated C ring instead of having a double bond in the C ring, with boron tribromide under the reaction conditions taught by Razdon and Zitko fails to provide isolable quantities of the corresponding trans isomer. In fact, it recently has been discovered that reaction of a 5-substituted resorcinol with 1-methoxy-4-(1-hydroxy-1-methylethyl)-1,4,-cyclohexadiene in the presence of excess boron trifluoride provides almost exclusively a cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibe nzo[b,d]pyran-9-one, without any isomerization to the trans isomer taking place under the conditions of the reaction. Such condensation reaction is the subject of Day and Lavagnino's copending application filed this even date herewith.
Certain of the trans-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-di benzo [b,d]-pyran-9-ones have recently been found to be of particular importance is pharmacological agents, especially in the treatment of anxiety, depression, and for producing analgesia. The use of such trans-hexahydrodibenzopyranones is described in detail in U.S. Pat. Nos. 3,928,598, 3,944,673, and 3,953,603. While the corresponding cis-hexahydrodibenzopyranones possess useful pharmacological activity, such activity is suprisingly somewhat less than that of the corresponding trans-isomers. It is therefore an object of this invention to provide a convenient process for converting a cis-hexahydrodibenzopyranone to the pharmacologically more active trans isomer.